On October 21, 2020 Genmab A/S (Nasdaq: GMAB) reported that positive topline results from the second part of the Phase 3 CASSIOPEIA (MMY3006) study of daratumumab monotherapy as maintenance treatment versus observation (no treatment) for patients with newly diagnosed multiple myeloma eligible for autologous stem cell transplant (ASCT) (Press release, Genmab, OCT 21, 2020, View Source [SID1234568731]). The second part of the study, which is being conducted by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen Research & Development, LLC (Janssen), met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.53 (95% CI 0.42 – 0.68), p < 0.0001) resulting in a 47% reduction in the risk of progression or death in patients treated with daratumumab. The safety profile observed in this study was consistent with the known safety profile of daratumumab and no new safety signals were observed.

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Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended to unblind the study results. Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, plans to discuss the potential for a regulatory submission for this indication with health authorities, and plans to submit the data to an upcoming medical conference and for publication in a peer-reviewed journal.

"Following the positive data from the first part of the CASSIOPEIA study, we are very pleased to see this benefit. We are appreciative of the efforts of the IFM, of HOVON and of Janssen for their work on this study," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the CASSIOPEIA (MMY3006) Study
This Phase 3 study is a randomized, open-label, multicenter study, conducted by the IFM in collaboration with the HOVON and Janssen, which includes 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who were eligible for high dose chemotherapy and ASCT. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide and dexamethasone (VTd) or VTd alone. The primary endpoint was the number of patients that achieved a stringent complete response (sCR). In the second part of the study, patients that achieved a response underwent a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) has become a backbone therapy in the treatment of multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with carfilzomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy; in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy7. Daratumumab is the first subcutaneous CD38 antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with multiple myeloma: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.8 DARZALEX FASPRO is the first subcutaneous CD38 antibody approved in the U.S. for the treatment of multiple myeloma.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,9,10,11,12

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase 3 studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

On October 21, 2020 Cellectis (Euronext Growth: ALCLS; Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported that it will report its financial results for the third quarter of 2020 together with a business update on Thursday, November 5, 2020, after the close of the US market (Press release, Cellectis, OCT 21, 2020, View Source [SID1234568730]). The announcement will be followed by a conference call at 8:00 AM EST / 2:00 PM CET on Friday, November 6, 2020, prior to the open of the US market.

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The live dial-in information for the conference call is:

US & Canada only: +1 (877) 407-3104
International: +1 (201) 493-6792
In addition, a replay of the call will be available until November 20, 2020 by calling +1 (877) 660-6853 (Toll Free US & Canada); +1 (201) 612-7415 (Toll Free International).
Conference ID: 13688263

On October 21, 2020 Biogen Inc. (Nasdaq: BIIB) reported third quarter 2020 financial results (Press release, Biogen, OCT 21, 2020, View Source [SID1234568728]).

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"In the third quarter, Biogen continued to execute on its strategy and delivered solid performance, although we began to face the launch of multiple generics of TECFIDERA in the U.S.," said Michel Vounatsos, Biogen’s Chief Executive Officer. "We look forward to participating in the aducanumab Advisory Committee meeting on November 6th, and we are excited about the prospect of aducanumab as a short- and long-term value creation opportunity. We have continued to allocate capital to create the opportunity for long-term shareholder value, including business development with our new collaboration in Parkinson’s disease."
Financial Results
•Third quarter total revenues were $3,376 million, a 6% decrease versus the third quarter of 2019, inclusive of a 1% unfavorable currency impact.
◦Multiple sclerosis (MS) revenues, including $272 million in royalties on sales of OCREVUS, decreased 4% versus the prior year to $2,257 million.
◦SPINRAZA revenues decreased 10% versus the prior year to $495 million.
◦Biosimilars revenues increased 13% versus the prior year to $208 million.
•Third quarter GAAP net income and diluted earnings per share (EPS) attributable to Biogen Inc. were $702 million and $4.46, respectively.
•Third quarter Non-GAAP net income and diluted EPS attributable to Biogen Inc. were $1,390 million and $8.84, respectively.
•GAAP R&D expenses in the third quarter of 2020 included a $601 million charge related to Biogen’s collaboration with Denali Therapeutics Inc. (Denali), which Biogen entered into in the third quarter of 2020 ($560 million upfront and a $41 million premium paid on Denali common stock purchased). These amounts are excluded from Non-GAAP R&D expense. Beginning in the third quarter of 2020, material upfront payments associated with significant collaboration and licensing arrangements are excluded from Non-GAAP R&D expense in order to better reflect the Company’s core operating performance. Year-to-date Non-GAAP results also reflect this change as the $125 million upfront payment related to the collaboration with Sangamo Therapeutics, Inc. (Sangamo) in the second quarter of 2020 has also now been excluded from Non-GAAP R&D expense.
Other Financial Highlights
•For the third quarter of 2020 GAAP and Non-GAAP net expense related to collaboration profit sharing was $73 million.
•For the third quarter of 2020 GAAP other expense was $129 million, primarily driven by net interest expense of $50 million and unrealized losses on strategic equity investments of $82 million. Non-GAAP other expense for the third quarter of 2020 was $46 million, primarily driven by net interest expense of $50 million partially offset by foreign exchange rate gains of $3 million.
•For the third quarter of 2020 the Company’s GAAP effective tax rate was approximately 25%, an increase from approximately 12% in the third quarter of 2019. This increase was primarily due to prior year favorability on Swiss tax reform as well as current year unfavorability, primarily driven by non-cash deferred tax adjustments related to TECFIDERA. For the third quarter of 2020 the Company’s Non-GAAP effective tax rate was approximately 18%, an increase from approximately 16% in the third quarter of 2019.
•In the third quarter of 2020 Biogen repurchased approximately 4.5 million shares of the Company’s common stock for a total value of approximately $1,250 million. The share repurchase program authorized in December 2019 was completed as of September 30, 2020.
•On October 20, 2020, Biogen’s Board of Directors authorized a program to repurchase up to $5.0 billion of the Company’s common stock (the 2020 Share Repurchase Program). The 2020 Share Repurchase Program does not have an expiration date. All shares repurchased under the 2020 Share Repurchase Program will be retired.
•As of September 30, 2020, Biogen had cash, cash equivalents, and marketable securities totaling $4,590 million and $7,425 million in notes payable. In the third quarter of 2020 the Company generated approximately $1,181 million in net cash flow from operations. Capital expenditures were
4

$84 million in the third quarter of 2020, and free cash flow, defined as net cash flow from operations less capital expenditures, was $1,097 million.
•For the third quarter of 2020 the Company’s weighted average diluted shares were 157 million.
2020 Financial Guidance
Biogen is providing an update to its full year 2020 financial guidance, which was last updated in July 2020 and assumed no generic entry for TECFIDERA. During the third quarter of 2020, the Company began to experience the impact of multiple TECFIDERA generic entrants in the U.S., and this financial guidance assumes significant erosion of TECFIDERA in the fourth quarter of 2020, the pace of which is difficult to predict. As a result, Biogen currently expects:

•2020 Full Year Revenue to be approximately $13.2 billion to $13.4 billion, compared to the prior guidance range of $13.8 billion to $14.2 billion.
•2020 Full Year GAAP diluted EPS to be between $25.50 and $26.50, compared to the prior guidance range of $32.00 to $34.00.
•2020 Full Year Non-GAAP diluted EPS to be between $32.50 and $33.50, compared to the prior guidance range of $34.00 to $36.00. This range excludes the upfront payments associated with the Sangamo and Denali collaborations during the second and third quarters of 2020, respectively.

This financial guidance does not include potential impacts from new acquisitions or large business development transactions, as both have elements that are hard to predict. This financial guidance assumes that foreign exchange rates as of September 30, 2020, remain in effect for the remainder of the year.
Biogen may incur charges, realize gains or losses, or experience other events or circumstances in 2020 that could cause actual results to vary from this financial guidance.

Recent Events
•In October 2020 Biogen submitted the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the review of aducanumab, an investigational treatment for Alzheimer’s disease. This MAA is subject to validation of whether the EMA accepts the application for review, which Biogen plans to announce when notified. Biogen is collaborating with Eisai Co., Ltd. (Eisai) on the development of aducanumab.
•In October 2020 Biogen entered into a collaboration with Scribe Therapeutics (Scribe) to develop and commercialize CRISPR-based therapies for the potential treatment of amyotrophic lateral sclerosis (ALS). Under the collaboration, Scribe will receive a $15 million upfront payment and may be eligible to receive up to $400 million in milestones as well as tiered high single digit to sub-teen royalties.
•In October 2020 Samsung Bioepis Co., Ltd. and Biogen announced that the EMA accepted for review the MAA for SB11, a proposed biosimilar referencing LUCENTIS (ranibizumab). Ranibizumab is an anti-VEGF (vascular endothelial growth factor) for retinal vascular disorders, which are a leading cause of blindness.
•In October 2020 Biogen announced that the Phase 2 AFFINITY study of opicinumab (anti-LINGO) in MS did not meet its primary or secondary endpoints and that Biogen has discontinued development of opicinumab.
•In September 2020 the U.S. Food and Drug Administration (FDA) announced that an advisory committee meeting of the Peripheral and Central Nervous System Drugs Advisory Committee will be held virtually on November 6, 2020, to review data supporting the Biologics License Application (BLA) for aducanumab. Background material and the link to the online teleconference meeting room will be available at View Source Scroll down to the appropriate advisory committee meeting link.
•In September 2020 Biogen dosed the first patient in a Phase 1 study of BIIB105, an antisense oligonucleotide targeting ataxin-2, in ALS.
•In September 2020 the first patient was dosed in Phase 3 AHEAD 3-45 clinical study of BAN2401, an anti-amyloid beta (Aβ) antibody, in individuals with preclinical Alzheimer’s disease who have intermediate or elevated levels of amyloid in their brains. Biogen is collaborating with Eisai on the development of BAN2401.
•In September 2020 Biogen announced Healthy Climate, Healthy LivesTM, a groundbreaking $250 million, 20-year initiative to eliminate fossil fuels across its operations and collaborate with renowned institutions with the aim to improve health, especially for the world’s most vulnerable populations. Building on its long-standing commitment to corporate responsibility, Biogen’s goal is to eliminate its fossil fuel emissions by 2040 as well as be a catalyst for positive change by advancing the science around how fossil fuels impact human health and taking action to promote climate and health equity.
•In September 2020 Biogen presented new data underscoring the efficacy and safety of its broad portfolio of MS therapies at MSVirtual2020, the eighth joint meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS). These presentations included new data further defining the effectiveness and safety profile of VUMERITY as well as new real-world MRI data suggesting that the effectiveness of extended interval dosing of TYSABRI is similar to the approved every-four-week dosing.
•In September 2020, also at MSVirtual2020, Biogen announced findings from a large, real-world study that provided insight into the clinical and health disparities that exist for people living with MS. Real-world data from the NARCRMS registry, a longitudinal database of more than 700 people living with MS in the U.S. and Canada, show that ethnic and racial disparities exist related to occupation, income status, MS-related disability, and type of treatment used.
•In August 2020 the first patient was dosed in the Phase 3 program for dapirolizumab pegol in patients with active systemic lupus erythematosus despite being treated by standard of care therapies. Dapirolizumab pegol is being developed in collaboration with UCB.
•In August 2020 the FDA accepted the BLA for aducanumab. The application was granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date on March 7, 2021, and the FDA has stated that, if possible, it plans to act early on this application under an expedited review.
•In August 2020 Biogen and Denali announced a collaboration to co-develop and co-commercialize Denali’s small molecule inhibitors of leucine-rich repeat kinase 2 (LRRK2), expanding Biogen’s pipeline of potential therapies in Parkinson’s disease. Biogen also received rights to opt into two programs and a right of first negotiation for two additional programs, in each case for neurodegenerative diseases leveraging Denali’s Transport Vehicle technology platform to cross the blood-brain barrier. Under the agreements, Denali received a $560 million upfront payment and an equity investment of $465 million and may be eligible to receive up to $1.125 billion in potential milestone payments, profit sharing, and royalties. The share purchase agreement and collaboration agreement subsequently closed in September 2020 and October 2020, respectively.

Conference Call and Webcast
The Company’s earnings conference call for the third quarter will be broadcast via the internet at 8:00 a.m. ET on October 21, 2020, and will be accessible through the Investors section of Biogen’s website, www.biogen.com. Supplemental information in the form of a slide presentation is also accessible at the same location on the internet and will be subsequently available on the website for at least one month.

On October 21, 2020 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, reported that it will host a conference call on Tuesday, October 27, 2020 at 5pm ET to discuss third quarter 2020 financial results and provide a corporate update (Press release, Ultragenyx Pharmaceutical, OCT 21, 2020, https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-host-conference-call-third-quarter-2020-financial [SID1234568726]).

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The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (International) and enter the passcode 4067577. The replay of the call will be available for one year.

On October 21, 2020 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported a paper published online in ACS Medicinal Chemistry Letters, a peer-reviewed publication of the American Chemical Society, titled, "Discovery of CA-4948, an Orally Bioavailable IRAK4 Inhibitor for Treatment of Hematologic Malignancies (Press release, Curis, OCT 21, 2020, View Source [SID1234568725])." The paper describes the preclinical work done to select CA-4948 and its on-target engagement and inhibition of IRAK4 in various animal studies. CA-4948 demonstrated potent IRAK4 inhibition, with favorable selectivity over other kinases, cellular activity, pharmacokinetics, efficacy, and safety, and showed tumor regression in a diffuse large B-cell lymphoma xenograft model without any overt toxicities.

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"We have been excited by the potential of CA-4948 since we began our partnership with its initial developer, Aurigene, in 2015," said James Dentzer, President and Chief Executive Officer of Curis. "This newly published paper further validates our confidence in CA-4948’s mechanism to selectively inhibit IRAK4 and its potential as a treatment for various hematologic malignancies. With our robust clinical development program for CA-4948 currently in Phase 1, we look forward to providing an update of clinical results for this program later this quarter."

About CA-4948

CA-4948 is a small molecule inhibitor of IRAK4, which is currently being tested in a Phase 1 dose escalating clinical trial in patients with non-Hodgkin lymphomas, including those with Myeloid Differentiation Primary Response 88 ("MYD88"), alterations. CA-4948 is also being investigated in a separate Phase 1 trial for acute myeloid leukemia and myelodysplastic syndromes. The Company is planning a combination study of CA-4948 and ibrutinib, a BTK inhibitor, in non-Hodgkin lymphomas with planned enrollment commencing in the fourth quarter of 2020.